Integrating Drug- and Formulation-Related Properties With Gastrointestinal Tract Variability Using a Product-Specific Particle Size Approach: Case Example Ibuprofen

J Pharm Sci. 2019 Dec;108(12):3842-3847. doi: 10.1016/j.xphs.2019.09.012. Epub 2019 Sep 17.

Abstract

In the present study, an in vitro-in vivo extrapolation of dissolution integrated to a physiologically based pharmacokinetics modeling approach, considering a product-specific particle size distribution and a self-buffering effect of the drug, is introduced and appears to be a promising translational modeling strategy to support drug product development, manufacturing changes and setting clinically relevant specifications for immediate release formulations containing ibuprofen and other weak acids with similar properties.

Keywords: absorption; dissolution; in vitro-in vivo (IVIVC) correlation(s); mechanistic modeling; particle size; physiologically based pharmacokinetic (PBPK) modeling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Chemistry, Pharmaceutical / methods
  • Drug Development / methods
  • Drug Liberation / drug effects
  • Gastrointestinal Tract / drug effects*
  • Humans
  • Ibuprofen / administration & dosage*
  • Ibuprofen / chemistry*
  • Models, Biological
  • Particle Size
  • Solubility / drug effects

Substances

  • Ibuprofen